EFFECTS OF MS-551, A NEW CLASS-III ANTIARRHYTHMIC DRUG, ON ACTION-POTENTIAL AND MEMBRANE CURRENTS IN RABBIT VENTRICULAR MYOCYTES

1 Electrophysiological effects of MS-551, a new class III antiarrhythmic drug, were examined and compared with those of (+)-sotalol in rabbit ventricular cells. 2 In rabbit ventricular muscles stimulated at 1.0 Hz, MS-551 (0.1-10 mum) and (+)-sotalol (3 100 mum) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization (V(max)). The class III effect of MS-551 was approximately 30 times more potent than that of (+)-sotalol. 3 Class III effects of MS-551 and (+)-sotalol showed reverse use-dependence, i.e., a greater prolongation of APD at a longer cycle length. 4 In rabbit isolated ventricular cells, 3 mum MS-551 and 100 mum sotalol inhibited the delayed rectifier potassium current (I(K)) which was activated at more positive potentials than - 50mV and saturated around + 20 mV. 5 MS-551 at a higher concentration of 10 mum decreased the transient outward current (I(to)) and the inward rectifier potassium current (I(K1)) although 100 mum sotalol failed to inhibit these currents. 6 MS-551 is a non-specific class III drug which can inhibit three voltage-gated K+ channels in rabbit ventricular cells.